Department of Pharmacy, Drug Delivery, Ludwig-Maximilians-University Munich, Munich, Germany.
Front Immunol. 2024 May 22;15:1389194. doi: 10.3389/fimmu.2024.1389194. eCollection 2024.
Past research has identified that cancer cells sustain several cancer hallmarks by impairing function of the endolysosomal system (ES). Thus, maintaining the functional integrity of endolysosomes is crucial, which heavily relies on two key protein families: soluble hydrolases and endolysosomal membrane proteins. Particularly members of the TPC (two-pore channel) and TRPML (transient receptor potential mucolipins) families have emerged as essential regulators of ES function as a potential target in cancer therapy. Targeting TPCs and TRPMLs has demonstrated significant impact on multiple cancer hallmarks, including proliferation, growth, migration, and angiogenesis both and . Notably, endosomes and lysosomes also actively participate in various immune regulatory mechanisms, such as phagocytosis, antigen presentation, and the release of proinflammatory mediators. Yet, knowledge about the role of TPCs and TRPMLs in immunity is scarce. This prompts a discussion regarding the potential role of endolysosomal ion channels in aiding cancers to evade immune surveillance and destruction. Specifically, understanding the interplay between endolysosomal ion channels and cancer immunity becomes crucial. Our review aims to comprehensively explore the current knowledge surrounding the roles of TPCs and TRPMLs in immunity, whilst emphasizing the critical need to elucidate their specific contributions to cancer immunity by pointing out current research gaps that should be addressed.
过去的研究已经确定，癌细胞通过损害内溶酶体系统（ES）的功能来维持几种癌症特征。因此，保持内溶酶体的功能完整性至关重要，这严重依赖于两个关键的蛋白质家族：可溶性水解酶和内溶酶体膜蛋白。特别是 TPC（双孔通道）和 TRPML（瞬时受体电位 mucolipins）家族的成员已成为 ES 功能的重要调节剂，是癌症治疗的潜在靶点。靶向 TPCs 和 TRPMLs 已证明对多种癌症特征具有重大影响，包括增殖、生长、迁移和血管生成。值得注意的是，内体和溶酶体也积极参与各种免疫调节机制，如吞噬作用、抗原呈递和促炎介质的释放。然而，关于 TPCs 和 TRPMLs 在免疫中的作用的知识还很缺乏。这引发了关于内溶酶体离子通道在帮助癌症逃避免疫监视和破坏方面的潜在作用的讨论。具体来说，了解内溶酶体离子通道与癌症免疫之间的相互作用变得至关重要。我们的综述旨在全面探讨 TPCs 和 TRPMLs 在免疫中的作用的现有知识，同时强调通过指出当前应解决的研究空白来阐明它们对癌症免疫的具体贡献的重要性。
